Estrogen receptor-α mediates estrogen facilitation of baroreflex heart rate responses in conscious mice

Jaya Pamidimukkala, Baojian Xue, Leslie G. Newton, Dennis B. Lubahn, Meredith Hay

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Abstract

Estrogen facilitates baroreflex heart rate responses evoked by intravenous infusion of ANG II and phenylephrine (PE) in ovariectomized female mice. The present study aims to identify the estrogen receptor subtype involved in mediating these effects of estrogen. Baroreflex responses to PE, ANG II, and sodium nitroprusside (SNP) were tested in intact and ovariectomized estrogen receptor-α knockout (ERαKO) with (OvxE+) or without (OvxE-) estrogen replacement. Wild-type (WT) females homozygous for the ERα+/+ were used as controls. Basal mean arterial pressures (MAP) and heart rates were comparable in all the groups except the ERαKO-OvxE+ mice. This group had significantly smaller resting MAP, suggesting an effect of estrogen on resting vascular tone possibly mediated by the ERβ subtype. Unlike the WT females, estrogen did not facilitate baroreflex heart rate responses to either PE or ANG II in the ERαKO-OvxE+ mice. The slope of the line relating baroreflex heart rate decreases with increases in MAP evoked by PE was comparable in ERαKO-OvxE- (-6.97 ± 1.4 beats·min -1·mmHg-1) and ERαKO-OvxE+ (-6.18 ± 1.3) mice. Likewise, the slope of the baroreflex bradycardic responses to ANG II was similar in ERαKO-OvxE- (-3.87 ± 0.5) and ERαKO-OvxE+(-2. 60 ± 0.5) females. Data suggest that estrogen facilitation of baroreflex responses to PE and ANG II is predominantly mediated by ERα subtype. A second important observation in the present study is that the slope of ANG II-induced baroreflex bradycardia is significantly blunted compared with PE in the intact as well as the ERαKO-OvxE+ females. We have previously reported that this ANG II-mediated blunting of cardiac baroreflexes is observed only in WT males and not in ovariectomized WT females independent of their estrogen replacement status. The present data suggest that in females lacking ERα, ANG II causes blunting of cardiac baroreflexes similar to males and may be indicative of a direct modulatory effect of the ERα on those central mechanisms involved in ANG II-induced resetting of cardiac baroreflexes. These observations suggest an important role for ERα subtype in the central modulation of baroreflex responses. Lastly, estrogen did not significantly affect reflex tachycardic responses to SNP in both WT and ERαKO mice.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number3 57-3
DOIs
StatePublished - Mar 2005
Externally publishedYes

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Keywords

  • Angiotensin II
  • Autonomic regulation
  • Cardiac baroreflexes
  • Hormone replacement

ASJC Scopus subject areas

  • Physiology

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